Collagen is the major fibrous protein of many animals. It accounts for about 30% of the total human body protein. Collagen constitutes the fibrillar component of the soft connective tissues (e.g., skin, ligament and tendon) and is the major component of the calcified tissues such as bone and dentin.
Collagen is composed of three proline/ hydroxyproline-rich polypeptide chains. There are known to be at least 12 genetically distinct forms of collagen. Four main types (I, II, III, and IV) have been characterized. Type I is the major portion of both soft and hard connective tissue. Type II collagen is the major collagen of cartilage. Type III is found in blood vessels, fetal membranes, and wounds. Basement membrane collagens are classified as type IV.
Injectable bovine collagen has been marketed for soft tissue augmentation since the early 1980s. This collagen is derived from bovine hide and is prepared by solubilizing the hide in acid, proteolytically digesting the soluble collagen to remove telopeptides, and purifying the atelopeptide collagen. The collagen is subsequently sterilized by submicron filtration and then reconstituted. Two forms of this collagen--one uncrosslinked and the other lightly crosslinked--are currently marketed under the trademarks ZYDERM.RTM. and ZYPLAST.RTM., respectively. Both forms comprise about 95% type I collagen and 5% type III collagen.
Human collagen has been proposed as a biomaterial for numerous indications, including soft tissue augmentation. Human collagen has the advantage of being less immunogenic than bovine-derived collagen. It has the disadvantage of requiring additional processing steps to ensure the elimination of human pathogens such as viruses.
U.S. 5,002,071 describes an injectable human collagen formulation for soft tissue augmentation in which the collagen is chorion and/or amnion collagen. The amnion/chorion is isolated from other placental tissues, homogenized, digested with proteases, reconstituted, and sterilized and crosslinked by gamma irradiation. The patent (col. 10, line 37 et seq.) indicates that the injectable human amnion collagen has a much larger proportion of type III collagen to type I collagen (43:57) than the bovine ZYDERM.RTM. and ZYPLAST.RTM. products. The patent and its prosecution history indicate that type III collagen has greater crosslinking than type I and is thus more persistent than type I.
The present invention relates to a collagen material that is derived from total placental tissue rather than just amnion/chorion tissue, is depleted of type III collagen to 10% by weight or below, and is sterilized by means other than irradiation. Contrary to the statements in U.S. 5,002,071, this type III depleted human collagen is more persistent than human collagen containing relatively large amounts of type III collagen.